Interleukin-2 is a cytokine with important regulatory properties for both T and B cells. The current studies were undertaken to evaluate interleukin-2 in the treatment of HIV infection. Our studies initially focused on patients with CD4 counts above 200 cells/mm3, administering IL- 2 for 5 days approximately every five months at doses ranging from 6 to 18 million. The courses of IL-2 were well-tolerated, although most of the patients required dosage reductions due to IL-2 related adverse effects. Sustained improved in CD4 number was seen in six of 10 patients, together with an increase in the proportion of cells (primarily CD4 positive cells) that are IL-2 receptor positive, and a decrease in the proportion of primarily CD8 cells that are HLA-DR positive. There also was a transient increase in viral load as measured by the bDNA assay seen at day 6-day 8 following initiation of IL-2 therapy. In a subsequent phase, no responses were seen in the patients with CD4 counts under 100 cells/mm3, although sustained evidence of viral activation as measured by both bDNA and p24 assays was detected. In the patients with CD4 counts between 100-200 cells/mm3, a minority have shown an improvement. Again, evidence of viral activation was seen. Over the past year we have more closely examined the charges in immune, viral, and cytokine profiles in 11 patients for 10 days after starting each round of IL-2. Based on the preliminary results seen in our open trial, we undertook a randomized trial to evaluate IL-2 therapy in patients with CD4 counts above 200 cells/mm3 in combination with currently approved antiretroviral therapies. The study opened in April 1993 and was completed in February of 1995, with 60 patients enrolling. Data analysis is currently underway. These studies are potentially important because they are the first ones to suggest that immunomodulating agents combined with antiretroviral agents may have a benefit in patients with HIV Infection, primarily those with CD4 counts above 200 cells/mm3.